应用微透析技术研究盐酸曲马多在小鼠额叶皮质细胞外液中的药动学  

Pharmacokinetics of tramadol hydrochloride in the extracellular fluid of mouse frontal cortex studied by in vivo microdialysis

作　　者：马张庆[1] 陶芳[1] 方浩[1] 许涛[1] 洪宗元[1] 

机构地区：[1]皖南医学院定量药理学研究所,药理学教研室,安徽芜湖241002

出　　处：《药学学报》2013年第3期406-410,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81171255);教育部科学技术研究重点项目(208058);安徽省自然科学基金资助项目(070413139)

摘　　要：研究盐酸曲马多在小鼠大脑额叶皮质细胞外液中的药动学,探讨靶器官药动学研究方法。小鼠麻醉后,将微透析探针植入其额叶皮质,以2μL.min 1速率向探针恒速灌注人工脑脊液。1 h后,小鼠腹腔注射盐酸曲马多注射液50 mg.kg 1,注射完毕立即以12 min为间隔收集额叶皮质细胞外液透析液样本,连续收集6 h。用HPLC-紫外检测法测定透析液中曲马多浓度,用DAS软件拟合药时曲线,并计算药动学参数。结果显示,曲马多在小鼠额叶皮质细胞外液中的变化过程呈二室开放模型,其主要药动学参数t1/2α、t1/2β、tmax、Cmax和AUC0∞分别为(0.27±0.05)h、(2.72±0.24)h、(0.50±0.10)h、(2 110.37±291.22)μg.L 1和(4 474.51±441.79)μg.L 1.h。本实验建立了一种应用微透析采样技术研究药物在靶器官中药动学的方法,该方法操作简单、可靠;盐酸曲马多在小鼠额叶皮质细胞外液中符合二房室模型,其分布半衰期和消除半衰期分别约为0.5 h和2.7 h。The paper aims to explore the studying method for the pharmaeokinetics of drugs in target organs, the pharmacokinetic process of tramadol hydrochloride in the extracellular fluid of frontal cortex （FrCx） of mice was investigated. Six male mice （Kunming strain） were anaesthetized （urethane, 1.8 g .kg-1, ip） and secured on a stereotaxic frame. A microdialysis probe was implanted into the FrCx and perfused with artificial cerebrospinal fluid at a flow rate of 2 pL.min-1. One hour later, mice were administrated （ip） with tramadol hydrochloride （50 mg.kg l） and dialysates were collected continuously at 12-min intervals （24 μL each） for 6 h. The tramadol concentration in dialysates was determined by HPLC-Ultraviolet detection method, and the concentration-time curve and pharmacokinetic parameters of tramadol were calculated with DAS software. The results showed that the pharmacokinetic process of tramadol in the FrCx extracellular fluid of mice was fitted to a two-compartment open model, and the main pharmacokinetic parameters tl/2a, tl/2B, tmax, Cmax and AUC0 were （0.27 ± 0.05） h, （2.72 ±0.24） h, （0.50 ± 0.10） h, （2 110.37 ±291.22） and （4 474.51 ± 441.79） respectively. In conclusion, a studying method for pharmacokinetics of drugs in the target organ is established, which is simple and feasible. Tramadol hydrochloride shows a two-compartment model in the extracellular fluid of the mouse FrCx, and the distribution- and elimination half-life are 0.5 h and 2.7 h, respectively.

关 键 词：曲马多 微透析 高效液相色谱 

分 类 号：R969[医药卫生—药理学]